This project is designed to assess the protective or anticarcinogenic effects of a supplement or deficiency of two nutrients, vitamin A and selenium, utilizing the methylbenzylnitrosamine (MBN) induced esophageal cancer model in the rat. This model, due to the organ specificity of MBN and its subchronic toxic effects, suggests 3 mechanisms by which to evaluate anticarcinogenic effects of these two factors: metabolism of the carcinogen, binding levels of the carcinogen and persistence of adducts, and the expression and growth of transformed cells. One or more of these mechanisms has been associated with the anticancer capabilities of these two compounds on chemical carcinogenesis. The mechanisms for anticarcinogenic effects will be explored by using HPLC technology, light and EM microscopy and autoradiography to determine the influence of the anticancer compounds on DNA synthesis, binding of MBN and adduct formation and removal from macromolecules of target (esophagus) and non-target (liver) tissues. An understanding of the basic mechanisms involved in anticarcinogenesis will permit the application of such information to the prevention of cancer in susceptible human populations by administration of the chemical compounds selenium and vitamin A, alone or in combination, under appropriate conditions.